Modeling and simulation of biochemical networks has become an essential activity to aid in the understanding of cellular behavior and to facilitate quantitative interpretation of modern experiments. A new approach, systems biology, is being advocated which combines modeling, simulation and quantitative experiments. Biomedical research is becoming increasingly dependent on construction and simulation of computational models. Arguably this will be even more the case with the development of personalized medicine. However, the technical aspects of modeling and simulation are overwhelming to a large number of biomedical researchers, and what is needed is a software application that is capable of providing the appropriate numerical algorithms shielded by a user interface that aides the biomedical researcher to conduct the required simulations. We propose to address this need with continuing development of our software COPASI, which is already widely used in the research community. This project will also provide support to the vibrant community of COPASI users/biomedical researchers. We will address this with the following Specific Aims: Aim 1: Enable COPASI with new functionality to provide advanced model capabilities by adding support for models containing noise and explicit time delays. Support for 1 and 2 dimensional compartments (filaments and membranes) will be implementes as well as support for discrete events in stochastic and delay differential simulation algorithms. Aim 2. Improve and extend interoperability and standards compliance. COPASI will be equipped to facilitate users to create and read simulation information in SED-ML format, it will be enabled to save and read simulation and experimental result in the SBRML format, and it will support the proposed SBML Level 3. Aim 3. Software maintenance. An existing testing plan will be continued and expanded, including appropriate collection models designed to test the various functions of the software; bug reports will be collected and fixed; suggestions for improvement will be collected from users and followed through. Aim 4. Support the modeling community. Online support will be developed and maintained, such as video tutorials, user forum, user manual, and frequently asked questions. A COPASI User's Workshop will be held annually. PUBLIC HEALTH RELEVANCE: This research will focus on developing and maintaining a computational tool, COPASI, for studying complex biological systems, including human disease models. This software application will facilitate knowledge discovery using computer simulations that are important in health and disease, including drug design. Use of this software will be available to all biomedical researchers and will contribute to understanding how diseases develop and how they can be cured.